Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The emerging biology of the nitrite anion

Nature Chemical Biology volume 1, pages 308–314 (2005)Cite this article

A Corrigendum to this article was published on 01 February 2006

Nitrite has now been proposed to play an important physiological role in signaling, blood flow regulation and hypoxic nitric oxide homeostasis. A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics.

On September 8th and 9th, 2005, a two-day symposium was held at the US National Institutes of Health (NIH) in Bethesda, Maryland, to address recent advances in our understanding of the role of nitrite in physiology, pathophysiology and therapeutics. The topics covered a wide breadth, including mechanisms of nitrite formation, transport, and enzymatic reduction to NO; nitrite as a substrate for nitration, nitrosation and nitrosylation reactions; the existence of a symbiotic 'nitrogen cycle' in humans; and the emerging role for nitrite in blood flow homeostasis, hypoxic vasodilatation, and therapeutics.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Nitrite chemistry, physiology and therapeutics.
Figure 2: Origin and interconversion of nitric oxide (NO) and nitrite (NO2−) and their role in cell signaling and gene expression.
Figure 3: Nitrite reductase activity of hemoglobin.
Figure 4: The human nitrogen cycle.

References

  1. Rodriguez, J., Maloney, R.E., Rassaf, T., Bryan, N.S. & Feelisch, M. Proc. Natl. Acad. Sci. USA 100, 336–341 (2003).

    Article  CAS  Google Scholar 

  2. Cosby, K. et al. Nat. Med. 9, 1498–1505 (2003).

    Article  CAS  Google Scholar 

  3. Bryan, N.S. et al. Nat. Chem. Biol. 1, 290–297 (2005).

    Article  CAS  Google Scholar 

  4. Zweier, J.L., Wang, P., Samouilov, A. & Kuppusamy, P. Nat. Med. 1, 804–809 (1995).

    Article  CAS  Google Scholar 

  5. Webb, A. et al. Proc. Natl. Acad. Sci. USA 101, 13683–13688 (2004).

    Article  CAS  Google Scholar 

  6. Duranski, M.R. et al. J. Clin. Invest. 115, 1232–1240 (2005).

    Article  CAS  Google Scholar 

  7. Bryan, N.S. et al. Proc. Natl. Acad. Sci. USA 101, 4308–4313 (2004).

    Article  CAS  Google Scholar 

  8. Wink, D.A. Nat. Med. 9, 1460–1461 (2003).

    Article  CAS  Google Scholar 

  9. Eiserich, J.P. et al. Nature 391, 393–397 (1998).

    Article  CAS  Google Scholar 

  10. Brennan, M.L. et al. J. Biol. Chem. 277, 17415–17427 (2002).

    Article  CAS  Google Scholar 

  11. Schopfer, F.J. et al. J. Biol. Chem. 280, 19289–19297 (2005).

    Article  CAS  Google Scholar 

  12. Schopfer, F.J. et al. Proc. Natl. Acad. Sci. USA 102, 2340–2345 (2005).

    Article  CAS  Google Scholar 

  13. Lundberg, J.O., Weitzberg, E., Lundberg, J.M. & Alving, K. Gut 35, 1543–1546 (1994).

    Article  CAS  Google Scholar 

  14. Benjamin, N. et al. Nature 368, 502 (1994).

    Article  CAS  Google Scholar 

  15. Millar, T.M. et al. FEBS Lett. 427, 225–228 (1998).

    Article  CAS  Google Scholar 

  16. Li, H., Samouilov, A., Liu, X. & Zweier, J.L. J. Biol. Chem. 279, 16939–16946 (2004).

    Article  CAS  Google Scholar 

  17. Huang, Z. et al. J. Clin. Invest. 115, 2099–2107 (2005).

    Article  CAS  Google Scholar 

  18. Kozlov, A.V., Staniek, K. & Nohl, H. FEBS Lett. 454, 127–130 (1999).

    Article  CAS  Google Scholar 

  19. Nagababu, E., Ramasamy, S., Abernethy, D.R. & Rifkind, J.M. J. Biol. Chem. (2003).

  20. Doyle, M.P., Pickering, R.A., DeWeert, T.M., Hoekstra, J.W. & Pater, D. J. Biol. Chem. 256, 12393–12398 (1981).

    CAS  Google Scholar 

  21. Huang, K.T. et al. J. Biol. Chem. 280, 31126–31131 (2005).

    Article  CAS  Google Scholar 

  22. Fernandez, B.O., Lorkovic, I.M. & Ford, P.C. Inorg. Chem. 42, 2–4 (2003).

    Article  CAS  Google Scholar 

  23. Marti, M.A., Crespo, A., Bari, S.E., Doctorovich, F.A. & Estrin, D.A. J. Phys. Chem. B 108, 18073–18080 (2004).

    Article  CAS  Google Scholar 

  24. Tocheva, E.I., Rosell, F.I., Mauk, A.G. & Murphy, M.E.P. Science 304, 867–870 (2004).

    Article  CAS  Google Scholar 

  25. Winterbourn, C.C. & Carrell, R.W. Biochem. J. 165, 141–148 (1977).

    Article  CAS  Google Scholar 

  26. Balagopalakrishna, C. et al. Biochemistry 37, 13194–13202 (1998).

    Article  CAS  Google Scholar 

  27. Kleinbongard, P. et al. Free Radic. Biol. Med. 35, 790–796 (2003).

    Article  CAS  Google Scholar 

  28. Dejam, A. et al. Blood 106, 734–739 (2005).

    Article  CAS  Google Scholar 

  29. Jensen, F.B. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 135, 9–24 (2003).

    Article  Google Scholar 

  30. Lauer, T. et al. Proc. Natl. Acad. Sci. USA 98, 12814–12819 (2001).

    Article  CAS  Google Scholar 

  31. Furchgott, R.F. & Bhadrakom, S. J. Pharmacol. Exp. Ther. 108, 129–143 (1953).

    CAS  Google Scholar 

  32. Gladwin, M.T. et al. Proc. Natl. Acad. Sci. USA 97, 11482–11487 (2000).

    Article  CAS  Google Scholar 

  33. Cannon, R.O., III et al. J. Clin. Invest. 108, 279–287 (2001).

    Article  CAS  Google Scholar 

  34. Crawford, J.H. et al. Blood published online 29 September 2005 (10.1182/blood-2005-07-2668).

  35. Hunter, C.J. et al. Nat. Med. 10, 1122–1127 (2004).

    Article  CAS  Google Scholar 

  36. Pluta, R.M., Dejam, A., Grimes, G., Gladwin, M.T. & Oldfield, E.H. J. Am. Med. Assoc. 293, 1477–1484 (2005).

    Article  CAS  Google Scholar 

  37. Lundberg, J.O., Weitzberg, E., Cole, J.A. & Benjamin, N. Nat. Rev. Microbiol. 2, 593–602 (2004).

    Article  CAS  Google Scholar 

  38. Tannenbaum, S.R., Weisman, M. & Fett, D. Food Cosmet. Toxicol. 14, 549–552 (1976).

    Article  CAS  Google Scholar 

  39. Bjorne, H.H. et al. J. Clin. Invest. 113, 106–114 (2004).

    Article  Google Scholar 

  40. Lundberg, J.O. & Govoni, M. Free Radic. Biol. Med. 37, 395–400 (2004).

    Article  CAS  Google Scholar 

  41. Binkerd, E.F. & Kolari, O.E. Food Cosmet. Toxicol. 13, 655–661 (1975).

    Article  CAS  Google Scholar 

  42. Hermann, L. Arch. Anat. Physiol. Lpz., 469–481 (1865).

  43. Brunton, T.L. Lancet ii, 97 (1867).

    Article  Google Scholar 

  44. Haldane, J. J. Hyg. (Lond.) 1, 115–122 (1901).

    Article  CAS  Google Scholar 

  45. Mitchell, H.H., Shonle, H.A. & Grindley, H.S. J. Biol. Chem. 24, 461–490 (1916).

    CAS  Google Scholar 

  46. Banham, H.A., Haldane, J.S. & Savage, T. Br. Med. J., 187–189 (1925).

  47. Brooks, J. Proc. R. Soc. Med. 123, 368–382 (1937).

    CAS  Google Scholar 

  48. Arnold, W.P., Mittal, C.K., Katsuki, S. & Murad, F. Proc. Natl. Acad. Sci. USA 74, 3203–3207 (1977).

    Article  CAS  Google Scholar 

  49. Green, L.C. et al. Proc. Natl. Acad. Sci. USA 78, 7764–7768 (1981).

    Article  CAS  Google Scholar 

  50. Green, L.C., Tannenbaum, S.R. & Goldman, P. Science 212, 56–58 (1981).

    Article  CAS  Google Scholar 

  51. Feelisch, M. & Noack, E.A. Eur. J. Pharmacol. 139, 19–30 (1987).

    Article  CAS  Google Scholar 

  52. Ignarro, L.J., Byrns, R.E. & Wood, K.S. in Vasodilation; Vascular Smooth Muscle, Peptides, Autonomic Nerves, and Endothelium (ed. Vanhoutte, P.M.) 427–435 (Raven, New York, 1988).

    Google Scholar 

  53. Furchgott, R.F. in Vasodilation; Vascular Smooth Muscle, Peptides, Autonomic Nerves, and Endothelium (ed. Vanhoutte, P.M.) 401–414 (Raven, New York, 1988).

    Google Scholar 

  54. Ignarro, L.J., Byrns, R.E., Buga, G.M. & Wood, K.S. Circ. Res. 61, 866–879 (1987).

    Article  CAS  Google Scholar 

  55. Palmer, R.M., Ferrige, A.G. & Moncada, S. Nature 327, 524–526 (1987).

    Article  CAS  Google Scholar 

  56. Hibbs, J.B., Jr., Taintor, R.R. & Vavrin, Z. Science 235, 473–476 (1987).

    Article  CAS  Google Scholar 

  57. Garthwaite, J., Charles, S.L. & Chess-Williams, R. Nature 336, 385–388 (1988).

    Article  CAS  Google Scholar 

  58. Marletta, M.A., Yoon, P.S., Iyengar, R., Leaf, C.D. & Wishnok, J.S. Biochemistry 27, 8706–8711 (1988).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank other session chairs, including H. Franklin Bunn, A. Butler, M. Doyle, D. Lefer, G. Mauk, C.S. Raman and J.L. Zweier, for their valuable scientific and organizational contributions to this meeting. This meeting was generously funded by the Office of Rare Diseases, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Neurological Disorders and Stroke and the Clinical Center of the National Institutes of Health. The meeting was also sponsored by the University of Pittsburgh School of Medicine, Wake Forest University, and the Medical College of Wisconsin. Additional information on speakers and presentations can be found at http://www.strategicresults.com/nitrite.

Author information

Authors and Affiliations

  1. Vascular Medicine Branch, National Heart, Lung, and Blood Institute,

    Mark T Gladwin

  2. the Critical Care Medicine Department, Clinical Center, US National Institutes of Health, Bethesda, Maryland, USA

    Mark T Gladwin

  3. National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland, USA

    Alan N Schechter

  4. Department of Physics, Wake Forest University, North Carolina, USA

    Daniel B Kim-Shapiro

  5. University of Alabama at Birmingham, Birmingham, Alabama, USA

    Rakesh P Patel & Jack R Lancaster Jr

  6. Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Neil Hogg

  7. Vascular Medicine Branch,

    Sruti Shiva & Richard O Cannon III

  8. Cardiovascular Branch, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA

    Sruti Shiva & Richard O Cannon III

  9. Heinrich-Heine-Universität, Düsseldorf, Germany

    Malte Kelm

  10. National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA

    David A Wink & Michael Graham Espey

  11. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, US National Institutes of Health, Bethesda, Maryland, USA

    Edward H Oldfield & Ryszard M Pluta

  12. Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Bruce A Freeman

  13. Boston University School of Medicine, Boston, Massachusetts, USA

    Martin Feelisch

  14. Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Jon O Lundberg

Authors
  1. Mark T Gladwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan N Schechter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel B Kim-Shapiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rakesh P Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neil Hogg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sruti Shiva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Richard O Cannon III
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Malte Kelm
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. David A Wink
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Graham Espey
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Edward H Oldfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ryszard M Pluta
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Bruce A Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jack R Lancaster Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Martin Feelisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jon O Lundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark T Gladwin.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gladwin, M., Schechter, A., Kim-Shapiro, D. et al. The emerging biology of the nitrite anion. Nat Chem Biol 1, 308–314 (2005). https://doi.org/10.1038/nchembio1105-308

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio1105-308

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing